GGT5
protein-codinggamma-glutamyltransferase 5, the group of Gamma-glutamyltransferases
Gene summary
This gene is a member of the gamma-glutamyl transpeptidase gene family, and some reports indicate that it is capable of cleaving the gamma-glutamyl moiety of glutathione. The protein encoded by this gene is synthesized as a single, catalytically-inactive polypeptide, that is processed post-transcriptionally to form a heavy and light subunit, with the catalytic activity contained within the small subunit. The encoded enzyme is able to convert leukotriene C4 to leukotriene D4, but appears to have distinct substrate specificity compared to gamma-glutamyl transpeptidase. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]
- GGTLA1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to GGT5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004121.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 2 | 5 | ||
| missense | 105 | 6 | 1 | 112 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 109 | 7 | 3 | 119 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004112.2 | 12 | MANE Select | |
| Ensembl | ENSP00000330080.4 | 12 | MANE Select | |
| RefSeq | NP_001093251.1 | 12 | Standard | |
| RefSeq | NP_001093252.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glutathione metabolism - Homo sapiens (human)
- Arachidonic acid metabolism - Homo sapiens (human)
- Taurine and hypotaurine metabolism - Homo sapiens (human)
- Glutathione metabolism
- Glutathione conjugation
Biological Process
- translation
- proteolysis
- cellular amino acid metabolic process
- glutamate metabolic process
- fatty acid metabolic process
Molecular Function
- peptidyltransferase activity
- leukotriene-C(4) hydrolase
- glutathione hydrolase activity
- hypoglycin A gamma-glutamyl transpeptidase activity
- leukotriene C4 gamma-glutamyl transferase activity
Cellular Component
- plasma membrane
- integral component of membrane
- intrinsic component of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398292
- Coding exons
- 12
- Length
- 25489
- Individuals with no LoFs
- 125688
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 59
- Defined
- 125747
- p
- 0.000235
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.690 | 315 | 351 | 0.896 | 0.0000215 | 3661 |
| Missense (PolyPhen) | 123 | 155.74 | 0.78978 | 1672 | ||
| Synonymous | -1.34 | 184 | 162 | 1.13 | 0.0000110 | 1268 |
| Loss of Function | 1.16 | 20 | 26.5 | 0.756 | 0.00000158 | 256 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00063 | 0.00062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00028 | 0.00026 | rare |
| South Asian | 0.00037 | 0.00036 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cleaves the gamma-glutamyl peptide bond of glutathione conjugates, but maybe not glutathione itself. Converts leukotriene C4 (LTC4) to leukotriene D4 (LTD4).;
Intolerance Scores
- LoFtool
- 0.822
- RVIS EVS
- -0.37
- RVIS percentile EVS
- 28.2
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.432
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |